What if the way to win the war on cancer is not to cure tumors but to keep them from forming in the first place? Dartmouth's Michael Sporn, known as the "father of chemoprevention," has devoted his career to that question. Now he and his collaborators have two compounds in clinical trials—compounds that may stop tumors before they start.

If an influenza pandemic strikes again, it could be cold comfort to know that lessons learned from the 1918 flu epidemic may offer more help than modern medicine. Here are some insights gleaned from the Dartmouth archives and from a Dartmouth graduate who studies pandemics.

Dartmouth Medicine was spawned in 1976, when the dictum "Don't trust anyone over thirty" was still in vogue. In the three decades since then—through one name change, several redesigns, many production improvements, and, most significantly, countless changes in its subject matter—the magazine has endeavored to earn the trust of readers, to engage you in Dartmouth medicine.

Looking at the function of a breast tumor—
how it behaves at the cellular and molecular
level—may increase the accuracy of
standard methods of screening for breast cancer,
which look for a tumor's form—a dense
mass of tissue. That's the hope of an interdisciplinary
team at Dartmouth.

Mammography remains the established
way of detecting and diagnosing breast cancer,
but there's growing recognition that the
technology is showing its age. Dartmouth
physicians and engineers have been collaborating
to develop a new generation of imaging
methods that examine how malignant tissue
behaves rather than its structure.

New: "This is all new ground. We're looking
beyond the usual anatomical thinking,"
says Steven Poplack, M.D., an associate professor
of radiology and principal author of a
paper to be published in a forthcoming issue
of Radiology. The study examined the electromagnetic
properties of abnormal and normal
breast tissue and found that abnormal tissue
(benign as well as malignant masses)
showed an increase in image contrast of
150% to 200% over normal tissue.

The three methods in the study look at
tissue's ability to scatter and absorb light,
store electricity, and conduct current:

Microwave imaging spectroscopy (MIS)
is sensitive to water content; it detects malignant
tumors because they have more water
and blood than normal tissue. The study
found that in subjects whose lesions were
larger than one centimeter, the predictive
value of mammography doubled with the addition
of MIS.

Near-infrared spectral tomography
(NIR) measures hemoglobin and oxygen saturation
in tissue. NIR was most effective in
identifying abnormal tissue greater than six
millimeters when looking at total hemoglobin
concentration. Brian Pogue, Ph.D., an associate
professor of engineering, is hopeful
that a hybrid NIR-MRI technique could be
used to monitor the effectiveness ofchemotherapy.

These experimental near-infrared images show (from the left)
the hemoglobin concentration, oxygenated hemoglobin saturation,
and percentage of water in the tissue of three breasts.

"That could make a difference
in diagnosing whether a patient
is responding to a particular
therapy," he explains. Dartmouth
is sharing its NIR data with a consortium
of research institutions
working on similar optical imaging
technologies.

Electrical impedance spectroscopy
(EIS) looks at how cells
conduct and store electricity. It was
able to distinguish between normal
and abnormal tissue, though it's
unclear yet if it can effectively differentiate
between cancer and other
abnormalities.

The three techniques were assessed individually
as well as by combining the properties
of all three. Results showed that the combined
analysis was a better predictor than any
individual method.

A fourth imaging technology is also being
developed at Dartmouth, but it hasn't been
investigated as thoroughly and so was not included
in the Radiology paper. Called magnetic
resonance elastography (MRE), it measures
the stiffness of tissue; malignant tumors
are harder and less elastic than normal breast
tissue. "It's like being able to take your hand
and feel locally where the stiffness is," says

Keith Paulsen, Ph.D., a professor of engineering
and principal investigator for the alternative
breast imaging research.

Pluses: Additional pluses of the new techniques
are that none of them use ionizing radiation
or require compression of the breast.
Instead, the subject lies prone on a special
examination table that has an opening for
the pendant breast, and a cross-section of the
tissue is exposed to different wavelengths or
frequencies of nonionizing radiation.
In addition to these four technologies prototyped
at Dartmouth, an unrelated system
being studied here has the potential to revolutionize
imaging in the shorter term. "Tomosynthesis
is probably much closer to commercialization,"
says Paulsen. "Many people
think it will replace mammography."

Tomosynthesis is an enhancement of digital
mammography; it involves taking multiple
low-dose exposures of the breast from different
angles. "The beauty of tomosynthesis
is it gives you this slice-by-slice look," says
Poplack. In a study of tomosynthesis as a diagnostic
tool, he showed it was just as good as
mammography at detecting cancer and had
fewer false positives. In a new multi-institutional
study, Dartmouth is now testing tomosynthesis
as a screening tool. Poplack expects
data analysis to begin in 2007.

Novel: Unlike tomosynthesis, Dartmouth's
alternative imaging techniques are unlikely
to replace mammography, but they do provide
novel information with the potential to
improve screening and diagnosis of breast
cancer. "Radiologists and clinicians have
never really looked at this kind of information
in the way we're providing it," says
Paulsen. The National Cancer Institute recently
expressed its confidence in the work
by awarding Paulsen's group $7.8 million in
continuing funding for the next five years.
Even so, actual clinical application of any
of the new methods is still in the distant future.
"New technology development is a long
row to hoe," says Poplack.

If you'd like to offer feedback about this article, we'd welcome getting your comments at DartMed@Dartmouth.edu.

This article may not be reproduced or reposted without permission. To inquire about permission, contact DartMed@Dartmouth.edu.